Objective: Economic analyses in reproductive medicine often fail to take into account the chances of treatment-independent conception. We compared the cost-effectiveness of several realistic strategies involving IVF using no treatment as the reference strategy. Design: A decision tree was constructed for a subfertile couple in which the clinician had to decide whether to offer treatment with IVF. No treatment at all was used as the reference strategy. Setting: An analytic decision-making framework. Patient(s): Hypothetical subfertile couples. Intervention(s): Two potential treatment approaches: three IVF cycles performed as soon as possible, or no treatment performed initially and then three or four IVF cycles performed if a pregnancy resulting in a live birth does not occur naturally after 2 1 2 years. Main Outcome Measure(s): The cost of establishing one pregnancy that results in a live birth. Result(s): The cost-effectiveness of IVF depended not only on the costs and expected success rates of IVF itself but also on the couple-specific chances of treatment-independent conception. Consequently, the cost-effectiveness of IVF is strongly dependent on the age of the female partner. This finding corresponds with everyday clinical experience. Conclusion(s): Economic analyses in reproductive medicine should take into account the option of providing no treatment.